Lipoprotein(a) Levels in Disaggregated Racial and Ethnic Subgroups Across Atherosclerotic Cardiovascular Disease Risk Levels.

Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Objectives: The authors assessed differences in Lp(a) testing and levels by disaggregated race, ethnicity, and ASCVD risk. Methods: This was a retrospective cohort study of patients from a large California health care system from 2010 to 2021. Eligible individuals were ≥18 years old, with ≥2 primary care visits, and complete race and ethnicity data who underwent Lp(a) testing. Race and ethnicity were self-reported and categorized as follows: non-Hispanic (NH) White, NH-Black, Hispanic (Mexican, Puerto Rican, other), NH-Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other). Logistic regression models tested associations between elevated Lp(a) (≥50 mg/dL) and race, ethnicity, and ASCVD risk. Results: 13,689 (0.9%) individuals underwent Lp(a) testing with a mean age of 54.6 ± 13.8 years, 49% female, 28.8% NH Asian. Over one-third of those tested had Lp(a) levels ≥50 mg/dL, ranging from 30.7% of Mexican patients to 62.6% of NH-Black patients. The ASCVD risk of those tested varied by race: 73.6% of Asian Indian individuals had <5% 10-year risk, whereas 27.2% of NH-Black had established ASCVD. Lp(a) prevalence ≥50 mg/dL increased across the ASCVD risk spectrum. After adjustment, Hispanic (OR: 0.76 [95% CI: 0.66-0.88]) and Asian (OR: 0.88 [95% CI: 0.81-0.96]) had lower odds of Lp(a) ≥50 mg/dL, whereas Black individuals had higher odds (OR: 2.46 [95% CI: 1.97-3.07]). Conclusions: Lp(a) testing is performed infrequently. Of those tested, Lp(a) levels were frequently elevated and differed significantly across disaggregated race and ethnicity groups. The prevalence of elevated Lp(a) increased with increasing ASCVD risk, with significant variation by race and ethnicity.

Comparative Metabolic Profiling of Different Colored Rice Grains Reveals the Distribution of Major Active Compounds and Key Secondary Metabolites in Green Rice.

Pigmented rice grains are important resources for health and nutritional perspectives. Thus, a thorough dissection of the variation of nutrients and bioactive metabolites in different colored rice is of global interest. This study applied LC-MS-based widely targeted metabolite profiling and unraveled the variability of metabolites and nutraceuticals in long grain/non-glutinous black (BR), red (RR), green (GR), and white rice (WR) grains. We identified and classified 1292 metabolites, including five flavonoid compounds specific to BR. The metabolite profiles of the four rice grains showed significant variation, with 275-543 differentially accumulated metabolites identified. Flavonoid (flavone, flavonol, and anthocyanin) and cofactor biosynthesis were the most differentially regulated pathways among the four rice types. Most bioactive flavonoids, anthocyanidins (glycosylated cyanidins and peonidins), phenolic acids, and lignans had the highest relative content in BR, followed by RR. Most alkaloids, amino acids and derivatives, lipids, and vitamins (B6, B3, B1, nicotinamide, and isonicotinic acid) had higher relative contents in GR than others. Procyanidins (B1, B2, and B3) had the highest relative content in RR. In addition, we identified 25 potential discriminatory biomarkers, including fagomine, which could be used to authenticate GR. Our results show that BR and RR are important materials for medicinal use, while GR is an excellent source of nutrients (amino acids and vitamins) and bioactive alkaloids. Moreover, they provide data resources for the science-based use of different colored rice varieties in diverse industries.

Characteristics of optic disc hemorrhage and optic nerve changes following acute primary angle closure.

Introduction: Acute primary angle closure (APAC) is an emergency ophthalmic presentation and a major cause of irreversible blindness in China. However, only a few studies have focused on the characteristics of optic disc hemorrhage (ODH) during an APAC attack, including its shape, depth, location, scope, and duration after intraocular pressure (IOP) control, along with changes in the optic nerve. This study aimed to analyze the characteristics of ODH and optic nerve changes in patients during their first APAC episode. Methods: This retrospective study involved 32 eyes from 32 patients with APAC who received sequential treatment and analyzed the following parameters: the highest IOP and its duration, ODH, retinal nerve fiber layer thickness (RNFLT), and mean deviation (MD). We compared parameters obtained from the affected eye (ODH group) and contralateral unaffected eye (control group), as well as intragroup comparisons. Results: The mean IOP in the ODH group was 64.28 ± 10.36 mmHg, with a duration of 4.44 ± 2.35 days. Flame and splinter shapes accounted for 84.38% of the ODH. The mean ODH duration was 4.81 ± 3.25 weeks. ODH during APAC was isolated to one sector in 59.38% of cases, mostly occurring in the temporal superior and temporal inferior (each accounting for 21.88% of the cases). There was a positive correlation between the extent of hemorrhage and the highest IOP duration (p < 0.001). RNFLT was significantly thickened within 72 h post-IOP control but was thinned by 2 weeks. By 6 months, the thinning stabilized, and there was no difference noted between the ODH and control groups at 12 months. MD partly improved at 6 months post-IOP control, and ODH scope significantly affected the MD (p < 0.001). The duration of high IOP was positively correlated to the ODH scope and MD damage. Discussion: Timely and effective IOP management is essential for recovering visual function following an APAC attack.

Transcatheter aortic valve replacement for aortic regurgitation: a systematic review and meta-analysis.

The efficacy and safety of new-generation devices (NGDs) for severe aortic regurgitation (AR) have mostly been based on single-arm studies with limited sample sizes. Our goal was to summarize the current evidence on NGDs and compare the safety and efficacy of 'off-label' and 'on-label' devices in NGDs. We searched MEDLINE, Embase, Cochrane Library, and Scopus for articles on transcatheter aortic valve replacement in patients with AR. A total of 31 studies that included 1851 patients were identified through April 2023. Among these, 1067 (57.6%) patients received treatment with 'on-label' devices (JenaValve and J-Valve). For NGDs, the total device success rate at 30 days was 94.5% (on-label: 97.8%, off-label: 89.9%; P < 0.001), the all-cause mortality was 4.2% (on-label: 2.6%, off-label: 5.1%; P = 0.006), permanent pacemaker implantation (PPI) was 8.8% (on-label: 6.9%, off-label: 18.4%; P < 0.001), and the rate of greater-than-mild paravalvular leak (PVL) was 1.2% (on-label: 0.9%, off-label: 3.8%; P = 0.003). On-label devices showed significantly better safety and efficacy in terms of the success rate, PPI, greater-than-mild PVL, and 30 day mortality than off-label devices.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

Surgeons' views of peer comparison and guideline-based feedback on postsurgery opioid prescriptions: a qualitative investigation.

BACKGROUND: Excess opioid prescribing after surgery can lead to prolonged opioid use and diversion. We interviewed surgeons who were part of a three-group cluster-randomised controlled trial aimed at reducing prescribed opioid quantities after surgery via two versions of a monthly emailed behavioural 'nudge' (messages encouraging but not mandating compliance with social norms and clinical guidelines around prescribing) at the end of the implementation year in order to understand surgeons' reasoning for changing or continuing their prescribing behaviour as a result of the intervention and the context for their rationale. METHODS: The study took place at a large healthcare system in northern California with surgeons from three surgical specialties-orthopaedics, obstetrics/gynaecology and general surgery. Following the intervention period, we conducted semistructured interviews with 36 surgeons who had participated in the trial, ensuring representation across trial arm, specialty and changes in prescribing quantities over the year. Interviews focused on reactions to the nudges, impacts of the nudges on prescribing behaviours and other factors impacting prescribing. Three study team members coded and analysed the transcribed interviews. RESULTS: Nudges were equally effective in reducing postsurgical opioid prescribing across surgical specialties and between intervention arms. Surgeons were generally receptive to the nudge intervention, noting that it reduced the size of their discharge opioid prescriptions by improving their awareness and intentionality around prescribing. Most were unaware that clinical guidelines around opioid prescribing existed. Some had reservations regarding the accuracy and context of information provided in the nudges, the prescription quantities encouraged by the nudges and feelings of being watched or admonished. A few described discussing the nudges with colleagues. Respondents emphasised that the prescribing behaviours are informed by individual clinical experience and patient-related and procedure-related factors. CONCLUSIONS: Surgeons were open to learning about their prescribing behaviour through comparisons to guidelines or peer behaviour and incorporating this feedback as one of several factors that guide discharge opioid prescribing. Increasing awareness of clinical guidelines around opioid prescribing is important for curbing postsurgical opioid overprescribing. TRIAL REGISTRATION NUMBER: NCT05070338.

Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity.

Objective: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. Methods: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. Results: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients. At 1 year after incident ASCVD, there was suboptimal statin use (any statins <60 %, high-intensity <25 %) and LDL-c control (<30 %) across groups, with lowest proportions in Black patients for statin use (46.7 %, any statin) and LDL-c control (10.7 %, OR 0.89 (0.81-0.97), referent NHW). Disaggregation of Asian and Hispanic groups unmasked within-group heterogeneity. Conclusions: In patients with incident ASCVD, we describe suboptimal and heterogenous 1-year post-ASCVD guideline-directed statin use and 1-year post-ASCVD LDL-c control across disaggregated race and ethnicity groups. Findings may improve understanding of ASCVD treatment disparities and guide implementation.

Peer Comparison or Guideline-Based Feedback and Postsurgery Opioid Prescriptions: A Randomized Clinical Trial.

Importance: Excess opioid prescribing after surgery can result in prolonged use and diversion. Email feedback based on social norms may reduce the number of pills prescribed. Objective: To assess the effectiveness of 2 social norm-based interventions on reducing guideline-discordant opioid prescribing after surgery. Design, Setting, and Participants: This cluster randomized clinical trial conducted at a large health care delivery system in northern California between October 2021 and October 2022 included general, obstetric/gynecologic, and orthopedic surgeons with patients aged 18 years or older discharged to home with an oral opioid prescription. Interventions: In 19 hospitals, 3 surgical specialties (general, orthopedic, and obstetric/gynecologic) were randomly assigned to a control group or 1 of 2 interventions. The guidelines intervention provided email feedback to surgeons on opioid prescribing relative to institutionally endorsed guidelines; the peer comparison intervention provided email feedback on opioid prescribing relative to that of peer surgeons. Emails were sent to surgeons with at least 2 guideline-discordant prescriptions in the previous month. The control group had no intervention. Main Outcome and Measures: The probability that a discharged patient was prescribed a quantity of opioids above the guideline for the respective procedure during the 12 intervention months. Results: There were 38 235 patients discharged from 640 surgeons during the 12-month intervention period. Control-group surgeons prescribed above guidelines 36.8% of the time during the intervention period compared with 27.5% and 25.4% among surgeons in the peer comparison and guidelines arms, respectively. In adjusted models, the peer comparison intervention reduced guideline-discordant prescribing by 5.8 percentage points (95% CI, -10.5 to -1.1; P = .03) and the guidelines intervention reduced it by 4.7 percentage points (95% CI, -9.4 to -0.1; P = .05). Effects were driven by surgeons who performed more surgeries and had more guideline-discordant prescribing at baseline. There was no significant difference between interventions. Conclusions and Relevance: In this cluster randomized clinical trial, email feedback based on either guidelines or peer comparison reduced opioid prescribing after surgery. Guideline-based feedback was as effective as peer comparison-based feedback. These interventions are simple, low-cost, and scalable, and may reduce downstream opioid misuse. Trial Registration: ClinicalTrials.gov NCT05070338.

Valorization and protection of anthocyanins from strawberries (Fragaria×ananassa Duch.) by acidified natural deep eutectic solvent based on intermolecular interaction.

This study introduces an innovative approach for the valorization and protection of anthocyanins from 'Benihoppe' strawberry (Fragaria × ananassa Duch.) based on acidified natural deep eutectic solvent (NADES). Choline chloride-citric acid (ChCl-CA, 1:1) was selected and acidified to enhance the valorization and protection of anthocyanins through hydrogen bond. The optimal conditions (ultrasonic power of 318 W, extraction temperature of 61 °C, liquid-to-solid ratio of 33 mL/g, ultrasonic time of 19 min), yielded the highest anthocyanins of 1428.34 µg CGE/g DW. UPLC-Triple-TOF/MS identified six anthocyanins in acidified ChCl-CA extract. Stability tests indicated that acidified ChCl-CA significantly increased storage stability of anthocyanins in high temperature and light treatments. Molecular dynamics results showed that acidified ChCl-CA system possessed a larger diffusion coefficient (0.05 m2/s), hydrogen bond number (145) and hydrogen bond lifetime (4.38 ps) with a reduced intermolecular interaction energy (-1329.74 kcal/mol), thereby efficiently valorizing and protecting anthocyanins from strawberries.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Extrachromosomal DNA in cancer.

Extrachromosomal DNA (ecDNA) has recently been recognized as a major contributor to cancer pathogenesis that is identified in most cancer types and is associated with poor outcomes. When it was discovered over 60 years ago, ecDNA was considered to be rare, and its impact on tumour biology was not well understood. The application of modern imaging and computational techniques has yielded powerful new insights into the importance of ecDNA in cancer. The non-chromosomal inheritance of ecDNA during cell division results in high oncogene copy number, intra-tumoural genetic heterogeneity and rapid tumour evolution that contributes to treatment resistance and shorter patient survival. In addition, the circular architecture of ecDNA results in altered patterns of gene regulation that drive elevated oncogene expression, potentially enabling the remodelling of tumour genomes. The generation of clusters of ecDNAs, termed ecDNA hubs, results in interactions between enhancers and promoters in trans, yielding a new paradigm in oncogenic transcription. In this Review, we highlight the rapid advancements in ecDNA research, providing new insights into ecDNA biogenesis, maintenance and transcription and its role in promoting tumour heterogeneity. To conclude, we delve into a set of unanswered questions whose answers will pave the way for the development of ecDNA targeted therapeutic approaches.

Cytotoxic and anti-inflammatory constituents from roots of Hypericum beanii and the antitumor potential under the view of cancer-related inflammation.

Hypericum beanii, a traditional folk medicine plant, has been employed in the treatment of various inflammation-related diseases and has demonstrated promising potential as an herbal remedy for cancer. In this study, we isolated 29 compounds from the roots of H. beanii. We evaluated their cytotoxic effects on five human cancer cell lines, which revealed that the ethanol extract, along with compounds 4 and 14, exhibited significant cytotoxic activity. Additionally, we assessed their anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that the ethanol extract (IC50 = 7.41 ± 0.38 µg/mL), compound 4 (IC50 = 7.82 ± 0.42 µM), and compound 14 (IC50 = 3.05 ± 0.06 µM) displayed substantial anti-inflammatory activity. ELISA assays and qPCR analysis revealed that compounds 4 and 14 may exert their anti-inflammatory and antitumor effects by inhibiting the expression of iNOS, TNF-α, IL-1ß, and IL-6 mRNA, shedding light on their role in cancer-related inflammation.

Revitalizing urban lake cleanup: optimizing flocculation and dewatering of dredged sludge using cation polyacrylamide.

This study investigated the effect of cation polyacrylamide (CPAM) on the dewatering performance of dredged sludge by batch experiments and compared it with a novel organic agent (DRC-300) and a traditional inorganic agent (PAC). The results of batch experiments suggested that the CPAM could promote the dewatering performance of dredged sludge inland lake. And at the dosage of 0.07% g/g suspended solids (SS), the moisture content of 37% could be achieved with CAPM. CPAM could reduce the sludge resistance filtration (SRF) and capillary adsorption time (CST) by 73% and 62%, respectively. Mechanism experiments revealed that CPAM improved the dewatering performance of dredged mud by increasing the sedimentation rate, accelerating the dissolution of organic matter, neutralizing the surface charge of sludge, and improving the void structure. Furthermore, CPAM outperformed DRC-300 and PAC in above aspects.

Nucleolar dynamics are determined by the ordered assembly of the ribosome.

Ribosome biogenesis is coordinated within the nucleolus, a biomolecular condensate that exhibits dynamic material properties that are thought to be important for nucleolar function. However, the relationship between ribosome assembly and nucleolar dynamics is not clear. Here, we screened 364 genes involved in ribosome biogenesis and RNA metabolism for their impact on dynamics of the nucleolus, as measured by automated, high-throughput fluorescence recovery after photobleaching (FRAP) of the nucleolar scaffold protein NPM1. This screen revealed that gene knockdowns that caused accumulation of early rRNA intermediates were associated with nucleolar rigidification, while accumulation of late intermediates led to increased fluidity. These shifts in dynamics were accompanied by distinct changes in nucleolar morphology. We also found that genes involved in mRNA processing impact nucleolar dynamics, revealing connections between ribosome biogenesis and other RNA processing pathways. Together, this work defines mechanistic ties between ribosome assembly and the biophysical features of the nucleolus, while establishing a toolbox for understanding how molecular dynamics impact function across other biomolecular condensates.

Extracts of Thesium chinense inhibit SARS-CoV-2 and inflammation in vitro.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading rapidly. Relevant research based on the antiviral effects of Thesium chinense Turcz (Santalaceae) was not found. OBJECTIVE: To investigate the antiviral and anti-inflammatory effects of extracts of T. chinense. MATERIALS AND METHODS: To investigate the anti-entry and replication effect of the ethanol extract of T. chinense (drug concentration 80, 160, 320, 640, 960 µg/mL) against the SARS-CoV-2. Remdesivir (20.74 µM) was used as positive control, and Vero cells were used as host cells to detect the expression level of nucleocapsid protein (NP) in the virus by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. RAW264.7 cells were used as an anti-inflammatory experimental model under lipopolysaccharide (LPS) induction, and the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The ethanol extract of T. chinense significantly inhibited the replication (half maximal effective concentration, EC50: 259.3 µg/mL) and entry (EC50: 359.1 µg/mL) of SARS-CoV-2 into Vero cells, and significantly reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. Petroleum ether (EC50: 163.6 µg/mL), ethyl acetate (EC50: 22.92 µg/mL) and n-butanol (EC50: 56.8 µg/mL) extracts showed weak inhibition of SARS-CoV-2 replication in Vero cells, and reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. CONCLUSION: T. chinense can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

Identification of NOL-Ring Composite Materials' Damage Mechanism Based on the STOA-VMD Algorithm.

This research utilized the sooty tern optimization algorithm-variational mode decomposition (STOA-VMD) optimization algorithm to extract the acoustic emission (AE) signal associated with damage in fiber-reinforced composite materials. The effectiveness of this optimization algorithm was validated through a tensile experiment on glass fiber/epoxy NOL-ring specimens. To solve the problems of a high degree of aliasing, high randomness, and a poor robustness of AE data of NOL-ring tensile damage, the signal reconstruction method of optimized variational mode decomposition (VMD) was first used to reconstruct the damage signal and the parameters of VMD were optimized by the sooty tern optimization algorithm. The optimal decomposition mode number K and penalty coefficient α were introduced to improve the accuracy of adaptive decomposition. Second, a typical single damage signal feature was selected to construct the damage signal feature sample set and a recognition algorithm was used to extract the feature of the AE signal of the glass fiber/epoxy NOL-ring breaking experiment to evaluate the effectiveness of the damage mechanism recognition. The results showed that the recognition rates of the algorithm in matrix cracking, fiber fracture, and delamination damage were 94.59%, 94.26%, and 96.45%, respectively. The damage process of the NOL-ring was characterized and the findings indicated that it was highly efficient in the feature extraction and recognition of polymer composite damage signals.

[Preparing for Pandemics]. / Vorbereitung auf eine Pandemie.

The current COVID-19 pandemic has contributed to millions of deaths globally and it is estimated that the hit to the global economy could reach more than twelve trillion US-dollars. Disease outbreaks have often pushed weak health systems to a breaking point, as witnessed during cholera, Ebola and Zika virus upsurges. The preparation of a plan involves the analysis of a scenario divided into the disaster cycle's four phases: preparation, response, recovery, and mitigation. Several levels of planning are recognised according to the goals to be reached: strategic plans are directed to define the organisational context and overall aims, operational plans with putting the strategy into place, tactical plans explain how resources will be allocated and managed, as well as provide essential instructions to the responders. The hospital surge capacity relies on the reorganisation of resources according to four categories: system, staff, stuff (supplies), and space. Each of these components needs to be analysed, implemented, and tested during the preparation phase to reduce the occurrence of a critical overrun of the response capabilities, as this will trigger the recourse of contingency plans. The response to pandemics must be associated with public health and social measures, as well as with initiatives to support the psycho-physical health of healthcare workers.

The transcriptomic landscape of normal and ineffective erythropoiesis at single-cell resolution.

The anemias of myelodysplastic syndrome (MDS) and Diamond Blackfan anemia (DBA) are generally macrocytic and always reflect ineffective erythropoiesis yet result from diverse genetic mutations. To delineate shared mechanisms that lead to cell death, we studied the fate of single erythroid marrow cells from individuals with DBA or MDS-5q. We defined an unhealthy (vs healthy) differentiation trajectory using transcriptional pseudotime and cell surface proteins. The pseudotime trajectories diverge immediately after cells upregulate transferrin receptor (CD71), import iron, and initiate heme synthesis, although cell death occurs much later. Cells destined to die express high levels of heme-responsive genes, including ribosomal protein and globin genes, whereas surviving cells downregulate heme synthesis and upregulate DNA damage response, hypoxia, and HIF1 pathways. Surprisingly, 24% ± 12% of cells from control subjects follow the unhealthy trajectory, implying that heme might serve as a rheostat directing cells to live or die. When heme synthesis was inhibited with succinylacetone, more DBA cells followed the healthy trajectory and survived. We also noted high numbers of messages with retained introns that increased as erythroid cells matured, confirmed the rapid cycling of colony forming unit-erythroid, and demonstrated that cell cycle timing is an invariant property of differentiation stage. Including unspliced RNA in pseudotime determinations allowed us to reliably align independent data sets and accurately query stage-specific transcriptomic changes. MDS-5q (unlike DBA) results from somatic mutation, so many normal (unmutated) erythroid cells persist. By independently tracking erythroid differentiation of cells with and without chromosome 5q deletions, we gained insight into why 5q+ cells cannot expand to prevent anemia.